Study of blood pressure drug valsartan retracted

matsubaraHiroaki Matsubara, a prominent cardiologist with five Expressions of Concern and two retractions for his CV, has another retraction.

As Larry Husten, who first reported the retraction at Forbes, notes, the notice for 2009’s “Effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high cardiovascular risks: KYOTO HEART Study,” which appeared in the European Heart Journal, says very little:

This article has been retracted by the journal. Critical problems existed with some of the data reported in the above paper. The editors of the European Heart Journal hereby retract this paper and discourage citations of it.

The study has been cited 62 times, according to Thomson Scientific’s Web of Knowledge.

From the original abstract:

Methods and results The KYOTO HEART Study was of a multicentre, Prospective Randomised Open Blinded Endpoint (PROBE) design, and the primary endpoint was a composite of fatal and non-fatal cardiovascular events ( NCT00149227). A total of 3031 Japanese patients (43% female, mean 66 years) with uncontrolled hypertension were randomized to either valsartan add-on or non-ARB treatment. Median follow-up period was 3.27 years. In both groups, blood pressure at baseline was 157/88 and 133/76 mmHg at the end of study. Compared with non-ARB arm, valsartan add-on arm had fewer primary endpoints (83 vs. 155; HR 0.55, 95% CI 0.42–0.72, P = 0.00001).

Conclusion Valsartan add-on treatment to improve blood pressure control prevented more cardiovascular events than conventional non-ARB treatment in high-risk hypertensive patients in Japan. These benefits cannot be entirely explained by a difference in blood pressure control.

Valsartan, marketed as Diovan, earned billions for Novartis and is now available as a generic. The FDA approved the drug, in a class known as angiotensin receptor blockers, or ARBs, for treatment of blood pressure, heart failure, and to extend life after a heart attack.

The European Society of Cardiology press-released the original study, and to their credit have noted the retraction in an update at the top of that release.

Husten, who has comments from a cardiologist who wrote an editorial questioning the original results, also asks whether many large randomized controlled clinical trials like this have been retracted. While we have reported on retractions of randomized studies, none were of this size.

Update, 8:30 a.m. Eastern, 2/6/13: Matsubara has made a statement on the matter (in Japanese). Thanks to Husten and a commenter for sending us the link.

9 thoughts on “Study of blood pressure drug valsartan retracted”

  1. Opaque retraction notice, so who knows what happened? Clearly this is important to know given the clinical implications of this case.

    1. As I have poor conduct of English, I cannot fully translate it into English.

      But I summerize his justification as follows:
      1. Two Cir J. articles and one EHJ article have “misrepresentations by carelessness” .
      2. These misrepresentations are due to typing error of “doctor(s) holding the post of data entry of the clinical trial”.
      3. As the number of misinput data is only 12, the conclusions of the articles are the same after the exclusion of those data.
      4. Kyoto heart study is non GCP trial which was planned in 2003.



  2. Forbes:
    Diovan Data Was Fabricated, Say Japanese Health Minister And University Officials

    The Mainichi:
    Data altered in Japanese research for Novartis blood pressure drug

    The Japan Times:
    Data in Novartis drug study manipulated

  3. Forbes: More Bad News For Novartis Blood Pressure Drug

    Another major study conducted in Japan– the Jikei Heart Study– will be retracted and Japanese health authorities said they were investigating severe skin reactions associated with use of the drug.

    Lancet. 2007 Apr 28;369(9571):1431-9. (will be retracted)
    Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study

    The Lancet, Volume 379, Issue 9824, Page e48, 14 April 2012
    Concerns about the Jikei Heart Study

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